The invention concerns a microsystem for the dielectric and optical manipulation of suspended particles, such as, for example, a fluid microsystem for the measurement and treatment of biological or synthetic particles, and further concerns the use of reflection shielding materials in microsystems, which material is designed to minimize the effect of electric and optical field forces on suspended particles.
Fluidic and liquid filled microsystems have multitudinous applications in biochemistry, medicine and biology, especially for the analysis and manipulation of dissolved substances or suspended particles. By means of the miniaturization and massive parallelism of the processes running in Microsystems (or microchips), particular advantages arise for the analysis and synthesis of biological macromolecules which are present in higher combinatorial multiplicity (refer to G. H. Sanders et al., in Trends in Analytical Chemistry, vol. 19/6, 2000, pg. 364 ff; W. Ehrfeld in Top ics in Current Chemistry, publisher A Manz et al., vol 194, Springer Verlag, 1988, pg. 233. ff). Applications in the fluidic microsystem especially encompass fundamental research, such as is found in DNA analysis or protein analysis, or even in active substance research including combinatorial chemistry. Further applications arise in the analysis and manipulation of individual biological cells or cell groups (see G. Führ et al., in Top ics in Current Chemistry, publisher A. Manz et al. vol. 194, Springer Verlag, 1998, pg. 83 ff).
Many applications of fluidic microsystems in cell biology, medicine, pharmaceuticals and biotechnology, are directed toward suspended particles, which are to be manipulated while subjected to the effects of electrical field forces (for instance, to evaluate, to measure, to divide, to move or to treat). The electrical field forces are produced with the aid of electrode arrangements of microelectrodes , which are specifically placed in accord with the application and the purpose of the task. The microelectrodes possess typical dimensions in the micromillimeter range. Other applications of microsystems are directed to the capture of the character of biological cells, which stand in direct contact with the microelectrodes (see, for example, B. I. Giaver et al., in Procedures of the National Academy of Sciences, vol. 88, 1991, pg. 7896, or refer to P. Fromherz et al., in Science vol. 252, 1991, pg. 1290.
An interest has developed, in the manipulation of microscopically small particles, of applying forces which are as independent as possible from electrical field influences. This effort has been described in Applied Physics A, by G. Fuhr, et al., vol. 67, 1998, page 385 and in Applied Physics B, by Th. Schnelle et al., Applied Physics B, vol 70, 2000, page 267.
In cell biology and molecular biology, with increasing frequency, particles are subjected to forces with the so-called laser-tweezers or with the UV-laser beam in microsurgery, wherein the said forces are generated by a focused illumination. Such forces are known as “optical forces”. The laser-tweezer (see A. Ashkin et al., in Nature, vol. 330, 1987, page 769) is based on the following principle:
A sharply focused laser beam is directed onto an objective with a high numerical aperture (>1), in a coaction zone, which, for instance, is to be found in a microsystem or another reservoir. Microparticles and especially biological cells in a range of size of from some 10 nm to some 10 μm are captured in the focus, and can be moved with displacement of the laser beam. In order that the beam loading be held as low as possible, especially on biological materials, the optical laser tweezers are operated at a wavelength in the range of 700 nm to 1064 nm. Optical tweezers are employed, for instance, for adhesion investigations on particles (refer to G. Fuhr. et al., in Trends in Analytical Chemistry, vol. 19/6, 2000, pg. 402, for positioning for fusion or poration-procedures on biological cells , see K. Schütze et al., in Cell. Mol. Biol., vol. 44/5, 1998, pg. 735) and in fluidic Microsystems with dielectrical particle manipulation, such as , for example dielectric field forces (G. Fuhr et al., Th. Schnelle et al., see above) or in rotation chambers (refer to DeGasperis, et al., in Meas. Sci. Technol., vol. 9, 1998, pg. 518).
The incident radiating of light is carried out in the case of Microsystems not only to achieve manipulation, but also for purposes of analysis. This involves a linking incidence of a laser beam to activate a fluorescence marker or to execute spectroscopic measurements on given particles.
A general problem present in the penetration of light into microsystems with electrode arrays is to be found therein, in that the electrodes can be heated by the said radiation. If, for example, a focused infrared laser beam invades or impacts the neighborhood (here in the micromillimeter range) of the surface of electrodes, this leads to a heating of the electrodes, more or less depending on the material of the electrode material and its inherent absorption and reflection characteristics. The result is often a localized buildup of gas bubbles (see A. Elshabini et al., in Thin Film Technology Handbook, McGraw-Hill Companies, 1998, ISBN 0-07-019025-9). Particularly strong absorption occurs with such materials as titanium, tantalum, and platinum. Not only the electrodes, but the contingent medium, such as the suspension liquid or a cell prone to adsorption are heated. This can lead to massive disturbances of the function of the microsystem under investigation.
For instance, in fluidic micro systems, which, for example, are energized for dielectrical particle manipulation with high frequency electrical voltages for the generation of higher field gradients (for instance, 1 kV/m, 1 Hz to 10 MHz), heating of electrodes can cause electro-hydro-dynamic flows within the suspension fluid, which are detrimental to, or indeed make fully impossible, a desired particle manipulation by the coaction of electric and optical field forces. Additionally, the formation of gas bubbles leads to stressing and destruction of the electrode material. Shock waves can be induced, which in turn burden the cells with undesirable pressure and current effects.
Corresponding problems also appear in Microsystems, in which the particles make direct contact with the electrodes. This event can cause local heating, under the action of which, for instance, cells sensitive to being adsorbed die off.
Thus the purpose of the invention is to make available an improved micro system for particle manipulation, which functions under the action of electrical and optical field forces, wherein the disadvantages of the conventional microsystems are overcome and in which, especially undesirable heating by external radiation of the electrodes is avoided, or reduced. The invented microsystem should make possible a reliable coaction of optical and electrical field forces on suspended particles without the formation of disturbing liquid movements.